Ginsenoside Rg1 protects mouse podocytes from aldosterone-induced injury in vitro

Abstract

Aim: Aldosterone is elevated in many diseases such as hypertension, diabetic nephropathy and chronic kidney disease, etc. The aim of this study was to investigate the effects of aldosterone on intracellular ROS production and autophagy in podocytes in vitro, and to explore the possibility of ginsenoside Rg1 (Rg1) being used for protecting podocytes from aldosterone-induced injury. Methods: MPC5 mouse podocyte cells were tested. Autophagosome and autophagic vacuole formation were examined under confocal microscopy with MDC and acridine orange staining, respectively. ROS were detected with flow cytometry. Malondialdehyde content and superoxide dismutase (T-SOD) activity were measured using commercial kits. The expression of LC3-II, beclin-1, SOD2 and catalase was measured by Western blotting. Results: Treatment with aldosterone (10 nmol/L) significantly increased ROS generation and the expression of SOD2 and catalase in MPC5 cells. Furthermore, treatment with aldosterone significantly increased the conversion of LC3-I to LC3-II, beclin-1 expression and autophagosome formation. Co-treatment with rapamycin (1 ng/mL) or chloroquine (10 μmol/L) further increased aldosterone-induced autophagosome formation. Co-treatment with Rg1 (80 ng/mL) effectively relieved oxidative stress and increased T-SOD activity at the early stage and subsequently decreased autophagy in aldosterone-treated podocytes. Co-treatment with 3-MA (4 mmol/L) or NAC (50 mmol/L) exerted similar effects against aldosterone-induced autophagy in podocytes. Conclusion: Aldosterone enhances ROS generation and promotes autophagy in podocytes in vitro. Ginsenoside-Rg1 effectively relieves aldosterone-induced oxidative stress, thereby indirectly inhibiting aldosterone-induced podocyte autophagy.

The roles of oxidative stress, endoplasmic reticulum stress, and autophagy in aldosterone/mineralocorticoid receptor-induced podocyte injury

“…Consistent with a recent study, 42 our data showed that autophagy was activated in podocytes by aldosterone. Previous studies have highlighted the essential role of Signaling pathway in podocyte injury Y Yuan et al autophagy for the cellular homeostasis of podocytes in health and disease.…”

The renoprotective role of autophagy activation in proximal tubular epithelial cells in diabetic nephropathy

“…The regulation of autophagy has been thought to be a major mechanism underlying numerous interventions for DN. In podocyte, aldosterone plays a pathogenic role in renal injury under conditions of DN, and aldosterone-treated mouse podocytes showed significantly increased the conversion of LC3-I to LC3-II, Beclin1 expression, indicating altered autophagy status (Mao et al, 2014). Maintenance of autophagy in podocytes was also suggested to be the mechanism by which histone deacetylase 4 inhibition ameliorates podocyte injury and attenuates glomerulopathy in DN .…”

Haplodeficiency of Klotho Gene Causes Arterial Stiffening via Upregulation of Scleraxis Expression and Induction of Autophagy

“…43–44 Accumulating evidence suggests that aldosterone may induce autophagy to remove protein aggregation. 45–46 However, whether autophagy causes extracellular matrix protein changes and contributes to arterial stiffening has never been investigated. We demonstrate that klotho deficiency upregulated autophagy in aortas which was mediated by aldosterone (Fig.…”